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| 10mg |
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| 25mg |
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AR-9281 is a novel and potent inhibitor of soluble epoxide hydrolase (s-EH) that can be potentially used for the treatment of hypertension and type 2 diabetes. s-EH is an essential enzyme in the metabolism of arachidonic acid, and has been implicated in the development of hypertension, inflammatory disease and metabolic abnormalities
| ln Vitro |
AR-9281 (APAU), with IC50 values of 13.8 nM and 1.7 nM, respectively, has inhibitory efficacy against human sEH (HsEH) and murine sEH (MsEH)[1].
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| ln Vivo |
AR-9281 (APAU) (oral, 150-200 mg/dL for 6 weeks) increases the therapeutic impact of EETs, slows the progression of hyperglycemia, protects myocyte structure, and lowers Ca2+ dysregulation and SERCA remodeling in hyperglycemic rats [2] .
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| Animal Protocol |
Animal/Disease Models: T2DM rat model [2]
Doses: 150-200 mg/dL Route of Administration: Oral (drinking) for 6 weeks Experimental Results: Attenuated the progressive increase in blood glucose concentration and preserved the mitochondrial structure and myogen of cardiomyocytes Fiber morphology. Protect intracellular Ca2+ effector system. There was less downregulation of sarco(end)oplasmic reticulum Ca2+ ATPase (SERCA) and lower expression of hypertrophy markers. |
| References |
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| Additional Infomation |
AR-9281 inhibits soluble epoxide hydrolase.
Drug Indication Investigated for use/treatment in hypertension. Mechanism of Action AR9281 inhibits soluble epoxide hydrolase (s-EH), an enzyme that plays a key role in the cytochrome P450 pathway of arachidonic acid metabolism. Nuclear factor alpha B (NF-alphaB) is a transcription factor implicated in cardiac hypertrophy, and can be anti or pro apoptotic under different conditions. Epoxyeicosatrienoic acids (EETs), a product of cytochrome P450 epoxygenase enzyme action, have a variety of anti-hypertensive and anti-inflammatory effects. EETs have a vasodilatory action similar to endothelium derived hyperpolarizing factor and may inhibit NF-alphaB through a currently unknown mechanism. The enzyme s-EH catalyzes the breakdown of EETs to dihydroxyeicosatrienoic acids. AR9281's inhibition of s-EH enhances EETs anti-hypertensive and anti-inflammatory activities by preventing their breakdown by s-EH, as well as inhibiting NF-alphaB. |
| Molecular Formula |
C18H29N3O2
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|---|---|
| Molecular Weight |
319.441764593124
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| Exact Mass |
319.225
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| CAS # |
913548-29-5
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| Related CAS # |
913548-29-5;
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| PubChem CID |
12000797
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
455
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC12CC3CC(C1)CC(C3)C2)NC1CCN(C(C)=O)CC1
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| InChi Key |
HUDQLWBKJOMXSZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H29N3O2/c1-12(22)21-4-2-16(3-5-21)19-17(23)20-18-9-13-6-14(10-18)8-15(7-13)11-18/h13-16H,2-11H2,1H3,(H2,19,20,23)
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| Chemical Name |
1-(1-acetylpiperidin-4-yl)-3-(1-adamantyl)urea
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~78.26 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1305 mL | 15.6524 mL | 31.3048 mL | |
| 5 mM | 0.6261 mL | 3.1305 mL | 6.2610 mL | |
| 10 mM | 0.3130 mL | 1.5652 mL | 3.1305 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00847899 | Completed | Drug: AR9281 Drug: AR9281 Drug: Placebo Drug: Placebo |
Hypertension Impaired Glucose Tolerance |
Arete Therapeutics | 2009-01 | Phase 2 |
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